A retrovirus is invading the Koala genome

21 April 2009

There are 62 koalas in Japanese zoos, and 50 of them are infected with koala retrovirus (KoRV). Infection may lead to leukemia and lymphoma, which could negatively impact Koala populations. What is the origin of KoRV?

The koala is native to Australia where they are found in eastern and southern coastal areas. All koalas in the eastern state of Queensland are infected with KoRV, while there are still some uninfected animals in the south. In particular, the koalas on Kangaroo Island do not carry the virus. Koalas were imported to Kangaroo Island in the early 1900s, and apparently those animals were free of KoRV. The island is 8 miles offshore which may contribute to the absence so far of the virus. However, the koalas sent to Japanese zoos likely carried KoRV.

Curiously, 38 koalas have been born in Japanese zoos since the original importation, and 36 of these animals are infected with KoRV. This high rate of infection is a consequence of the fact that KoRV DNA integrates into DNA of koala germ cells. The viral genome is transmitted vertically, from mother to offspring.

The nucleic acid of retroviruses is RNA, but it is converted to a DNA copy during infection and integrates into host cell DNA. If the viral DNA integrates into the germ line, then it can remain in the organism for many generations. The genomes of most higher organisms contain remnants of retroviral genomes called endogenous retroviruses (ERVs). In primates these infections appear to have occurred millions of years ago; in humans, they comprise 6-8% of the genome, more than protein coding sequences (1-2%)! Most ERVs are defective but the koala ERVs are unique because they appear to produce viral particles.

No one has ever observed germ-line infection of a species with retroviruses – until infection of koalas with KoRV was discovered. This process of ‘endogenization’ can now be studied in real time.

When did the KoRV begin invading the koala genome? It has been suggested that the initial infection occurred less than 100 years ago, but examination of preserved Koala DNA will be required to confirm this estimate.

The origin of most ERVs is unknown because the original infecting viruses disappeared long ago. But it might be feasible to identify the precursor of KoRV, which entered the genome relatively recently. KoRV appears to be closely related to an ERV of the Asian mouse Mus caroli. If this relationship is correct it will have to be determined how the virus was transmitted from mice in Southeast Asia to koalas in Australia.

Infection with KoRV in captive animals may lead to fatal lymphomas or immunosuppression and chlamydial infection. It is possible that infection of wild animals might lead to further decreases in this dwindling population. Should a KoRV vaccine developed to prevent extinction? Development and testing of a vaccine would require the use of koalas. It’s a difficult question, because the spread of KoRV among koalas is a natural part of evolutionary selection. Should we interfere?

There do not appear to be any effects on germ cells by the integrated KoRV genome. It's not clear that these integrated copies are producing infectious virus: “The koalas that have been examined so far have very high levels of circulating KoRV in the blood (viremia), and it is not at all clear whether this results simply from reactivation of recently acquired germline proviruses or whether the animals have also been infected by exogenously transmitted KoRV.”

Is there an estimate for how often retroviruses embed into mammalian genomes? We know there was a “burst” of ERV embeddings since the chimpanzee/human split, but it's possible this is atypical, as humans are.

If mus caroli has an ERV now which is very close to be infectious in another species, can one conjecture that the ERV was also infectious in mus caroli recently? Maybe we're unlucky in having just missed a retroviral invasion in a lab-sized species, rather than being lucky in witnessing it in a rather large species now. Or maybe we haven't looked at mouse populations closely enough.

Is there an estimate for how often retroviruses embed into mammalian genomes? We know there was a “burst” of ERV embeddings since the chimpanzee/human split, but it's possible this is atypical, as humans are.

If mus caroli has an ERV now which is very close to be infectious in another species, can one conjecture that the ERV was also infectious in mus caroli recently? Maybe we're unlucky in having just missed a retroviral invasion in a lab-sized species, rather than being lucky in witnessing it in a rather large species now. Or maybe we haven't looked at mouse populations closely enough.

If you want to see a génome invasion by a retrovirus in a lab species you can have a look at gypsy in drosophila melanogaster…..
And by the way Korv is not yet a real endogenous retrovirus because to achieve this you have to be fix in the population and maybe this one is to pathogène to be…